Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/52861
標題: Cdk5蛋白對於多囊性卵巢疾病之扮演角色的探討 (WR2)
Investigation of the Roles of Cdk5 Protein in Poly Cystic Ovary Syndrome (WR2)
作者: 林赫
關鍵字: 基礎研究
poly cystic ovary syndrome, Cdk5, p35, thecal cells
其他(醫)
多囊性卵巢
Cdk5蛋白
p35蛋白
鞘細胞
摘要: 多囊性卵巢症候群是一種好發於女性的常見疾病,通常被認為與雄性激素分泌異常有關,同時亦常伴隨著高胰島素血症的出現,此病徵可能導致病患日後出現如糖尿病、高血壓等慢性疾病,實為一個需要重視的疾病。另一方面,Cdk5蛋白在中樞神經系統發育及神經退化性疾病(如阿茲海默症)中扮演的角色於近年來被踴躍地討論。本實驗室自成立以來致力於探討Cdk5蛋白在人類各系統中的未知功能。已發表之研究成果顯示Cdk5蛋白對於髓質性甲狀腺癌細胞生長及癌化扮演重要角色;Cdk5蛋白於攝護腺癌細胞中可受到藥物過度活化而導致癌細胞凋亡。94年度國科會計畫成果指出,Cdk5蛋白經由調控StAR蛋白(steroidogenic acute regulatory protein)的穩定性而正向促進萊氏細胞之雄性激素生物合成途徑。此外,有文獻指出Cdk5蛋白對於胰島β細胞分泌胰島素亦有調控的功能。綜合以上的線索,本計畫的目的在利用分子生物及分子藥理學的方法配合離體細胞模式及活體動物模式,探討Cdk5蛋白是否於多囊性卵巢症候群中,扮演了雙重影響卵巢鞘細胞(thecal cells)異常分泌雄性激素及胰臟胰島素的異常分泌。主要的進行方法是利用已建立的鞘細胞離體初級培養方法,配合Cdk5蛋白相關工具,如抑制劑、siRNA抑制合成(knock-down)、或是轉染之過度表現(overexpression)。除此之外,我們意欲利用大鼠多囊性卵巢模式,活體及離體分別探討Cdk5蛋白的重要性。最後,希望將多囊性卵巢症候群之常見的高胰島素血症應用至Cdk5蛋白相關現象,瞭解抑制Cdk5蛋白於體內是否可同時影響鞘細胞及胰臟β細胞的分泌而達到抑制多囊性卵巢的症狀。雖然活體動物的實驗冗長且結果難料,但希望本計畫研究成果能盡力詮釋Cdk5蛋白於多囊性卵巢症候群扮演之角色,同時也為治療該類疾病開起一個新的契機。
Poly cystic ovary syndrome (PCOS) is a common disease in female. It is believed that PCOS is correlated to aberrant secretion of androgen and hyperinsulinemia and also causes the following chronic diseases, such as diabetes and hypertension. Therefore, this issue is worthy to be concerned. On the other hand, Cdk5 is enthusiastically discussed about its roles in central nervous development and neurodegeneration (such as Alzheimer』s disease). Recently, our lab made efforts in exploring the novel roles of Cdk5 in different human tissues. The published results demonstrated that Cdk5 plays an important role in tumorigenesis of medullary thyroid carcinoma cells. In addition, drug-induced Cdk5 overactivation was also found to cause apoptosis of prostate cancer cells. The preliminary results of 2005-NSC grant indicated that Cdk5 could phosphorylate StAR protein which enhanced its stability and subsequently stimulated the steroidogenesis in Leydig cells. Furthermore, it has also been identified that Cdk5 modulates the insulin secretion in pancreatic β cells. Therefore, the goal of this grant is to investigate the possible dual roles of Cdk5 in PCOS on both aberrant secretions of androgen and insulin by the approaches of cell biology, molecular pharmacology, and in vivo experiments. The main tools for us are to use the in vitro primary culture of ovarian thecal cells and Cdk5-related manipulation, such as inhibitor, siRNA, and overexpression. Besides, we will also try to use PCOS animal model to verify the importance of Cdk5. Finally, the role of Cdk5 inhibition to treat PCOS through blocking both secretions of thecal androgen and pancreatic insulin is the most important issue to be addressed. Although the in vivo experiments are complicated and the results are unexpected, we hope our efforts can shed light on the roles of Cdk5 in PCOS and also contribute to its new therapeutic strategy.
URI: http://hdl.handle.net/11455/52861
其他識別: NSC96-2629-B005-001
文章連結: http://grbsearch.stpi.narl.org.tw/GRB/result.jsp?id=1489082&plan_no=NSC96-2629-B005-001&plan_year=96&projkey=PF9611-0216&target=plan&highStr=*&check=0&pnchDesc=Cdk5%E8%9B%8B%E7%99%BD%E5%B0%8D%E6%96%BC%E5%A4%9A%E5%9B%8A%E6%80%A7%E5%8D%B5%E5%B7%A2%E7%96%BE%E7%97%85%E4%B9%8B%E6%89%AE%E6%BC%94%E8%A7%92%E8%89%B2%E7%9A%84%E6%8E%A2%E8%A8%8E+%28WR2%29
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